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Most hereditary coagulation disorders other than hemophilia are rare autosomal recessive conditions that cause disease only in homozygous people (see Table 1: Coagulation Disorders: Screening Laboratory Test Results in Inherited Defects in Blood Coagulation ). Factor XI deficiency is uncommon in the general population but common in descendants of European Jews (gene frequency about 5 to 9%). Bleeding typically occurs after significant injuries, including trauma or surgery, in people who are homozygotes or compound heterozygotes.
Severe deficiency of α2-antiplasmin (1 to 3% of normal), the major physiologic inhibitor of plasmin, can also cause bleeding. Diagnosis is based on a specific α2-antiplasmin assay. ε-Aminocaproic acid or tranexamic acid is used to control or prevent acute bleeding. Heterozygous people with α2-antiplasmin levels of 40 to 60% of normal can occasionally experience excessive surgical bleeding if secondary fibrinolysis is extensive (eg, in patients who have had open prostatectomy).
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Table 1
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| Screening Laboratory Test Results in Inherited Defects in Blood Coagulation |
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Screening Test Results*
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Defect
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Comments
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PTT long
PT normal
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Factor XII, high molecular weight kininogen, or prekallikrein
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Laboratory test abnormality without clinical bleeding
Must be distinguished from factor XI deficiency, in which posttraumatic and perioperative bleeding may occur, by specific assays
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PTT long
PT normal
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Factor XI
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Autosomal recessive
Increased frequency in Ashkenazi Jews
Posttraumatic and perioperative bleeding
Diagnosis by specific assay
For bleeding: Fresh frozen plasma 5–20 mL/kg/day to keep factor XI level > 30%
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PTT long
PT normal
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Factor VIII or IX
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Factor VIII deficiency (hemophilia A)
Factor IX deficiency (hemophilia B)
X-linked transmission
Mild or severe bleeding in males, depending on factor VIII or IX level
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PTT normal
PT long
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Factor VII
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Autosomal recessive
Rare
If deficiency is severe (< 2%), serious bleeding
If levels are > 5%, mild or no bleeding
Therapy of choice: Recombinant factor VIIa
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PTT long
PT long
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Factor X, V, or prothrombin
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Autosomal recessive
Rare
Mild to severe bleeding
Diagnosed by specific assays
For bleeding episodes due to factor X or prothrombin deficiency: Fresh frozen plasma or prothrombin complex concentrate
For treatment of factor V deficiency: Fresh frozen plasma with or without platelet concentrates (to supply platelet factor V)
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In afibrinogenemia (fibrinogen < 10 mg/dL), no clotting in PTT or PT because machine end point is not triggered
In hypofibrinogenemia (fibrinogen 70–100 mg/dL), PTT and PT often prolonged by several seconds and thrombin time long
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Fibrinogen
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Severe bleeding in afibrinogenemia (homozygous state)
Posttraumatic and perioperative bleeding in hypofibrinogenemia (heterozygous state)
For treatment: Cryoprecipitate (5–10 bags, with each containing about 250 mg fibrinogen)
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PTT and PT long
Thrombin time long
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Dysfibrinogenemia
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Various manifestations (no or only mild, posttraumatic and perioperative bleeding, tendency for thrombosis, wound dehiscence)
Fibrinogen low in clotting assay but normal in immunologic assay
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PTT normal
PT normal
Thrombin time normal
Clot lysis in 5M urea
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Factor XIII
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Autosomal recessive
Rare
Poor wound healing
Spontaneous abortions in women
Severe bleeding when levels are < 1% of normal
For treatment: Fresh frozen plasma (1–2 units q 4–6 wk is effective because half-life of factor XIII is about 10 days)
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PTT and PT normal
Clot lysis times in 5M urea or saline accelerated
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α 2-Antiplasmin deficiency
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Severe bleeding in homozygotes
Posttraumatic and perioperative bleeding in heterozygotes
Specific assay required for confirmation of diagnosis
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*PT results are typically reported as INR.
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Last full review/revision June 2009 by Joel L. Moake, MD
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